Methods of forming a C—C bond between two different compounds each having a C—H bond continues to be of keen interest to the pharmaceutical and fine chemical industries. Namely, the formation of the C—C bond by first breaking the two C—H bonds and then forming a bond between the two carbons is particularly desirable given ready accessibility of hydrocarbon compounds, atom efficiency, and reduced production cost. The formation of the C—C bond may be illustrated by the following chemical equation:R1—C—H+H—C—R2→R1—C—C—R2 
Methods of forming C—C bonds from C—H bonds are known to be difficult as C—H bonds are only modestly reactive under mild conditions. One way to overcome the difficulty is to introduce an intermediate step of first functionalizing or “activating” the C—H bond using a transition metal catalyst and then reacting the functionalized C—H bond with another compound. Functionalization of the C—H bond involves substituting the hydrogen atom with a different functional group. Preferably, the functional group forms a more reactive bond with the carbon such that the carbon becomes more reactive to form different chemical bonds in subsequent reactions.
To date, functionalization of C—H bonds have focused primarily on formation of C—B, C—C, C—N, and C—O bonds with much less attention paid to coupling the carbon to heavier atoms. For example, one of the most commonly used methods involves formation of a C—B bond by use of boron chemistry. The “functionalized” C—B bond may subsequently be utilized in a Imamura-Suzuki coupling reaction to create a C—C bond as exemplified in the following chemical equation where each of R1 and R2 comprises a hydrocarbon moiety:
The foregoing use of boron chemistry to create the C—C bond suffers a number of disadvantages including low product yields and limited scope of application, especially in the presence of incompatible functional groups. It is therefore desirable to have a new and improved method to functionalize a C—H bond which avoids the disadvantages of boron chemistry.
It is of note that a new and improved method to functionalize a C—H bond would have valuable applications in synthesis of fluorinated compounds. Fluorinated compounds are considered to be important compounds in the pharmaceutical and agrochemical sectors due to their increased resistance to metabolic degradation and increased lipophilicity. Fluorinated compounds also find use as important parts in a number of polymers, membrane, and semi-conductor materials.
Traditionally, to synthesize a particular fluorinated compound, fluorination is performed at a final stage of chemical synthesis to convert a non-fluorinated intermediate to the desired fluorinated compound. Such approach suffers the disadvantages of being limited by the chemistry of fluorination and the high costs associated with fluorination. Therefore, it would be advantageous to instead begin the synthesis with a fluorinated intermediate, and then subject the fluorinated intermediate to subsequent reactions to obtain the desired fluorinated compound. Such approach is particularly advantageous as a number of fluorinated intermediates or starting compounds are commercially available.
To synthesize the desired fluorinated compound from the fluorinated intermediate, the subsequent reactions may advantageously incorporate functionalization of a C—H bond of the fluorinated intermediate. For example, the C—H bond may be functionalized and converted to a C—Sn bond. The carbon of the C—Sn bond may subsequently be utilized in a well-developed Stille coupling reaction to form a bond with another carbon as exemplified in the following chemical reaction where each of R and R′ comprises a hydrocarbon moiety:R—Sn(R)3+R′—X→R—R′+X—Sn(R)3 Such combination of functionalization of a C—H bond and subsequent reaction of the functionalized bond to form a C—C bond may readily be incorporated as part of synthesis of a wide variety of commercially useful fluorinated compounds.
Currently, a number of fluorinated intermediate compounds with a functionalized C—Sn bond are commercially available. Such compounds include 2,3,4,5,6-pentafluorophenyltrimethylstannane and bis(pentafluorophenyl)dimethylstannane. Other fluorinated intermediate compounds such as 2,3,5,6-tetrafluorophenyltrimethylstannane, 2,3,4,6-tetrafluorophenyltrimethylstannane, and (2,3,4-trifluorophenyl)trimethylstannane are known but are not commercially available on any reasonable scale. Such fluorinated compounds are often made using methods that are expensive (and involving use of organomagnesium, organolithium and organotinhalide compounds), leads to a limited range of products, and which involve multiple steps performed at high temperatures with poor product yield.
Therefore, it is desirable to find a novel and improved method to synthesize fluorinated intermediate compounds with a functionalized C—Sn bond, which is simple and commercially viable with high product yields and which avoids use of expensive and harmful reagents.